DEERFIELD, Ill.--(BUSINESS WIRE)-- Baxter International Inc. (BAX) today announced that the United States Food and Drug Administration (FDA) granted approval of Baxter’s FEIBA [Anti-Inhibitor Coagulant Complex], the first and only FDA-approved treatment for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B who have developed inhibitors.

Inhibitor development is considered one of the most serious complications associated with hemophilia treatment today. As many as one-third of previously untreated patients with severe or moderately severe hemophilia A are at risk for developing inhibitors, which are antibodies produced by the body’s immune system in response to factor replacement treatment. The presence of an inhibitor makes response to treatment more challenging, and patients with inhibitors have an increased risk of developing complications.

The approval is based on data from a pivotal Phase III study, known as FEIBA PROOF, in which treatment with a FEIBA prophylactic regimen showed a 72 percent reduction in median annual bleed rate (ABR) compared to treatment with an on-demand regimen. In the intent-to-treat (ITT) analysis, three of the 17 (18%) adult patients in the prophylactic arm reported no bleeding episodes. The most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting. The serious adverse reactions seen with FEIBA are hypersensitivity reactions and thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

''The PROOF study demonstrated that a prophylactic regimen with FEIBA can significantly reduce the rate of bleeding episodes, as compared to an on-demand regimen, in hemophilia patients with inhibitors. This is important among these patients who often have difficult-to-treat bleeds and are at risk of additional complications,'' said Steven Pipe, M.D., Director, Division of Pediatric Hematology and Oncology, at the C.S. Mott Children’s Hospital at the University of Michigan. ''This FDA approval of a prophylactic regimen should change the way physicians think about managing hemophilia with inhibitors, validating FEIBA prophylaxis as an effective new option to treat their patients.''

Pro-FEIBA, a prospective investigator-initiated, randomized, crossover study published in the New England Journal of Medicine in 2011 showed a 62 percent reduction in all bleeding episodes with FEIBA prophylaxis compared to an on-demand regimen. Together with the data from the FEIBA PROOF study, the results provide valuable evidence that prophylaxis with FEIBA can significantly reduce bleeding rates when compared to on-demand treatment.

''FEIBA has been an effective treatment for hemophilia patients with inhibitors for more than 35 years as an on-demand treatment. FEIBA was first licensed in the US as FEIBA VH and then as FEIBA NF. This additional indication for prophylactic treatment is aimed at reducing the number of bleeds among this patient population,'' said Ludwig Hantson, Ph.D., president of Baxter’s BioScience business. ''This latest approval reflects our legacy of offering new approaches to help reduce the disease burden of hemophilia, and supports Baxter’s ongoing commitment to pursuing a bleed-free world.''

FEIBA is approved in more than 60 countries worldwide and is indicated for prophylaxis in more than 40 countries.

FEIBA PROOF Study Details

The prospective, open label, randomized, multi-center, two-arm parallel study investigated the efficacy and safety of FEIBA prophylactic treatment compared to on-demand treatment in 36 patients with hemophilia A or B with inhibitors over a 12-month period. The most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting. The occurrence of hepatitis B surface antibodies has been seen in other plasma-derived products and could be due to the passive transfer of antibodies following FEIBA treatment. None of the subjects showed any signs of active hepatitis B infection.

Known anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components, including factors of the kinin generating system

Disseminated intravascular coagulation (DIC)

Acute thrombosis or embolism (including myocardial infarction)

Thromboembolic events (including venous thrombosis, pulmonary embolism, myocardial infarction, and stroke) can occur with FEIBA, particularly following the administration of high doses (above 200 units per kg per day) and/or in patients with thrombotic risk factors.

Infusion of FEIBA should not exceed a dose of 100 units per kg body weight every 6 hours and daily doses of 200 units per kg body weight. Monitor patients receiving more than 100 units per kg of body weight of FEIBA for the development of DIC, acute coronary ischemia and signs and symptoms of other thromboembolic events. If clinical signs or symptoms occur, such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain, discontinue the infusion and initiate appropriate diagnostic and therapeutic measures.

Hypersensitivity and allergic reactions, including severe anaphylactoid reactions, can occur following the infusion of FEIBA. The symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. These reactions can be severe and systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported. If signs and symptoms of severe allergic reactions occur, immediately discontinue administration of FEIBA and provide appropriate supportive care.

Because FEIBA is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Hemophilia is a rare genetic blood clotting disorder that primarily affects males.1 People living with hemophilia do not have enough of, or are missing, one of the blood clotting proteins naturally found in blood.1 Two of the most common forms of hemophilia are A and B.2 In people with hemophilia A, clotting factor VIII (FVIII) is not present in sufficient amounts or is absent.2 Without enough FVIII, people with hemophilia can experience spontaneous, uncontrolled internal bleeding that is painful, debilitating, damaging to joints and potentially fatal.2 People with hemophilia B (also called Christmas disease) do not have sufficient amounts of clotting factor IX.2 In about 30% of cases, there is no family history of hemophilia and the condition is the result of a spontaneous gene mutation.3 According to the World Federation of Hemophilia, it is estimated that more than 400,000 people in the world have hemophilia.2 All races and economic groups are affected equally.1 It is estimated that approximately 17,000 people in the U.S. have been diagnosed with hemophilia A or B.4

About Inhibitors

As many as one-third of previously untreated patients with severe or moderately severe hemophilia A are at risk for developing inhibitors,5,6,7 which are antibodies produced by the body’s immune system in response to factor replacement treatment.8,9 The presence of an inhibitor makes response to treatment more challenging, and patients with inhibitors have an increased risk of developing complications such as joint damage.10 Inhibitors cause the body to work against the factor replacement treatment, neutralizing its effect and preventing an individual’s blood from clotting.10,11 Individuals who have inhibitors have a form of hemophilia that is more difficult to control, with an increased risk of uncontrolled bleeding, compared to patients without inhibitors. Inhibitor development is considered one of the most serious complications associated with hemophilia treatment, and may include other associated complications such as impaired movement, increased need for surgery and greater complexity or risk associated with surgery.12,13

About Baxter International Inc.

Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, cancer, infectious diseases, kidney disease, trauma and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.